Project 4: Carbon Nanotube-based Microbeam Radiation Therapy for Human Brain Cancer We will develop a nanotechnology-enabled compact microbeam radiation therapy (MRT) system and translate the promising experimental radiotherapy from animal research to widespread clinical application. State-of-the-art radiotherapy today provides excellent benefits for many patients with radiosensitive cancers. However, these benefits greatly diminish for patients with radioresistant tumors, such as brain cancers. For these patients the radiafion, needed to eradicate the tumor is so toxic that it can cause intolerable damage to normal tissues. An ultimate radiotherapy approach should have high tissue type selectivity - it intrinsically eradicates tumor while leaving normal tissue function intact. MRT may be just such a radiotherapy approach. Convincing animal studies show that a single MRT treatment of ultrahigh dose (100s Gy) eradicates tumor without functional damage to normal tissue including that of the developing central nervous system. Despite its enormous potential MRT has not been used on human. There are two major bottlenecks In translating MRT from bench-side to bedside: 1) the lack of comprehensive understanding of the underlying mechanism and 2) the lack of accessible MRT irradiation devices. There are only synchrotron-based animal research MRT systems In the world, and no human MRT system exists today. Our goal is to develop a nanotechnology-based compact human MRT system for human brain tumors, especially glioblastoma (GBM), The poor control of GBM by current radiafion therapy is related to the dose limiting normal brain tissue damage such as brain necrosis. We hypothesize that MRT can effectively eradicate human brain tumors including GBM without severe normal brain function damage. We therefore propose to develop a compact MRT system for human brain cancers. The key technical challenge is to achieve the signature high dose rate at the microbeam spatial distribution. Our approach is to utilize the carbon nanotube based spatially distributed multi-beam field emission x-ray technology that was pioneered by our team. During the first CCNE project the technology blossomed into a technologically and commercially attractive approach for medical imaging and radiotherapy applications. In this second CCNE project we will use the CNT field emission technology to design the first nonsynchrotron-facility-based MRT system targeted for human brain cancer. We will validate that the CNTbased MRT radiation produces similar radiobiological effects on small animals as the synchrotron based MRT system. We will design, simulate, and validate major components of the compact human MRT system. Our target is to have the complete human MRT system design ready for device fabrication.